MDMA-like stimulus effects of hallucinogens in male Fawn-Hooded rats.
A two-lever, food-motivated, operant technique was employed to train the purportedly serotonergically dysfunctional Fawn-Hooded (FH) rat to discriminate 1.5 mg/kg MDMA. Once all 10 male subjects learned the MDMA-vehicle discrimination at criterion performance level, doses different than the training dose were used to generate a dose-response discrimination gradient. The ED50 value of MDMA was shown to be 0.136 mg/kg, not significantly different from that of previously trained Sprague-Dawley male rats. Thus, the Fawn-Hooded rat appears to not differ in its sensitivity to lower doses of MDMA. Testing for MDMA-like stimulus generalizations with other drugs indicated that the MDMA derivative MDE produced generalization at a dose of 2.25 mg/kg and allowed for an ED50 value of 0.496 mg/kg. Like MDE, the testing of alpha-ethyltryptamine was shown to produce MDMA-like responding. Lastly, a dose of 0.12 mg/kg LSD produced 90% MDMA-lever selection. In contrast to MDMA generalizations to these three drugs, testing of cocaine at doses of 2.5-10 mg/kg and mescaline at 8-14 mg/kg did not produce MDMA-like discriminative effects. The results of this testing in the presumably serotonergically dysfunctional Fawn-Hooded rat would indicate that this line not only can discriminate MDMA as well as heterogenous-bred lines, but also shows the same discriminative generalizations and nongeneralizations from MDMA to serotonergic and dopaminergic agents.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095, USA.
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004192:Discrimination, Psychological / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000235:genetics / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D006213:Hallucinogens; D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine